Lung cancer is a major cause of mortality and morbidity worldwide. Overall survival has only improved slightly despite advances in surgery, radiotherapy, and chemotherapy. Molecularly targeted agents are currently being studied in all treatment settings including that of chemoprevention, which is defined as the use of natural or synthetic agents to interrupt the process of carcinogenesis and to prevent or delay tumour occurrence. Lung cancer has become an increasingly difficult problem to treat with standard therapies and chemopreventive strategies have been developed. Progress in chemoprevention is reliant on the collaborative efforts of researchers in basic science and clinical settings who study the biology of lung cancer with the goal of uncovering new mechanisms of carcinogenesis. Small molecules which target specific receptors or mutations such as inhibitors of epidermal growth factor receptor or RAS will have an increasingly significant role as they are associated with more tolerable side-effects and may prove more effective. Development of a risk model with intermediate endpoints is essential for future chemoprevention studies.